Offspring Of Parents Research Articles

P179 CARDIOMETABOLIC DYSFUNCTIONS IN THE OFFSPRING OF FRUCTOSE-OVERLOADED RATS: EVIDENCE FOR THE CHOLINERGIC ANTI-INFLAMMATORY REFLEX

Background: Studies have reported an increase in the consumption of processed foods high in fructose (F), which has been associated with the development of metabolic syndrome. The cholinergic anti-inflammatory reflex (CAT) pathway appears to play an important role in this condition. This study investigated the role of the CAT pathway by splenic and vagal denervation (D) and treatment with galantamine (GAL) on cardiometabolic and autonomic parameters in the offspring of rats subjected to chronic fructose consumption. Methods: Wistar rats (parents) were given fructose (10% drinking water) or water for 60 days. The rats were then mated and the fructose overload was maintained for females until the end of lactation. The offspring were randomized into 4 groups (n=10/5 per sex): Control (C), F, F+GAL, and F+D+GAL. GAL (5 mg/kg), an acetylcholinesterase inhibitor, was administered 30 days by gavage. D was performed at 21 days. The offspring were evaluated at 51 days. Results: Compared with the C group (3.63±0.24 mg/dl/%/min), the F and F+D+GAL groups (2.8±0.20 and 2.9±0.14 mg/dl/%/min) had a worsening of insulin sensitivity. The F+GAL (370±79 mg) and F+D+GAL groups (310±75 mg) had reduced adipose tissue compared to the C (708±121 mg) and F (980±160 mg) groups. The F and F+D+GAL groups (vs. C group) had increased mean arterial pressure (AP) (114±1.9 and 115±1.4 vs. 101±2.2mmHg), heart rate (381±5 and 369±5 vs. 343±10bpm), and low frequency component of systolic AP (4.95±0.49 and 3.33±0.23 vs. 1.62±0.2mmHg2). The F+GAL group had an increase in cardiac vagal modulation (HF-PI and RMSSD). F and F+D+GAL groups (vs. C) had impairment of baroreflex (-3.24±0.26 and -3.48±0.1 vs. -3.93±0.1bpm/mmHg), and F+GAL group improved this parameter. Conclusion: Our data provide evidence for the involvement of CAT in cardiometabolic dysfunction in the offspring of parents exposed to chronic fructose consumption. Such findings highlight the importance of therapeutic strategies that improve autonomic modulation to prevent early changes in offspring of metabolically overburdened parents. Financial support: FAPESP(2022/04050-1), CNPq, CAPES-PROSUP.

Exploring the importance of family socio-economic position on the association between parental BMI and offspring BMI trajectories

PurposeWe aimed to investigate the associations between parental BMI and offspring BMI trajectories and to explore whether the parent-offspring BMI growth trajectory association differed according to family SEP or social mobility. MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Children’s weight and height were collected from 1 to 18 years. Parents’ height and weight were reported pre-pregnancy. We assessed family SEP by measuring parents’ and grandparents’ educational attainment, social class, and social mobility by changes in education attainment across generations. Multilevel models were used to develop trajectories and assess patterns of change in offspring BMI, to associate parental BMI with these trajectories, and explore whether these associations differed by family SEP and social mobility. Results13,612 children were included in the analyses. The average BMI of offspring whose parents were overweight or obese was higher throughout childhood and adolescence, compared to those with parents of normal BMI. Parental and grandparental low SEP were associated with higher child BMI, but there was little evidence of modification of parent-offspring associations. For example, at age 15 years the predicted mean BMI difference between children of overweight or obese mothers versus normal-weight mothers was 12.5 % (95 %CI: 10.1 % to 14.7 %) and 12.2 % (95 %CI: 10.3 % to 13.7 %) for high and low grandparental SEP, respectively. DiscussionThese findings strengthen the evidence that higher parental BMI and lower family SEP were associated with higher offspring BMI, but we did not observe strong evidence that family SEP modifies the parental-offspring BMI association.

Hypothalamic-pituitary-adrenal axis functioning in offspring of parents with a major affective disorder: a meta-analytic review.

Because the offspring of parents with an affective disorder (OAD) are at high risk for developing mental disorders, and persons with an affective disorder (AD) show dysfunctional hypothalamic-pituitary-adrenal (HPA) axis activity, changes in HPA functioning in OAD might be an etiological risk factor that precedes the development of ADs. The primary aim of the meta-analysis was to quantitatively summarize the existing data on different indices of diurnal cortisol in the OAD. The secondary aim was to explore potential moderators of this relation. Following PRISMA guidelines, we included 26 studies (3052 offspring) on diurnal cortisol in our meta-analysis after an initial screening of 3408 articles. Intercept-only and meta-regression models were computed using the robust variance estimation method. Analyses examining mean cortisol levels at discrete timepoints, total cortisol output, and the cortisol rise in response to awakening (CAR) were conducted separately. The results demonstrated that the OAD had higher mean levels of cortisol at different timepoints throughout the day compared to controls (Hedge's g = 0.21). There was evidence of publication bias in studies examining CAR, such that effect sizes were positively biased. The present findings are consistent with a meta-analysis showing elevated cortisol in youth having an AD. Notable limitations across studies include the method of cortisol measurement and assessment of ADs. Altogether, these results highlight the fact that increased cortisol levels may act as a potential neuroendocrine antecedent and/or risk factor for the development of ADs among high risk youth.

Transgenerational effects of stress on reproduction strategy in the mixed mating plant Lamium amplexicaule

BackgroundThe theory of Condition Dependent Sex predicts that – everything else being equal – less fit individuals would outcross at higher rates compared with fitter ones. Here we used the mixed mating plant Lamium amplexicaule, capable of producing both self-pollinating closed flowers (CL), alongside open flowers (CH) that allow cross pollination to test it. We investigated the effects of abiotic stress – salt solution irrigation – on the flowering patterns of plants and their offspring. We monitored several flowering and vegetative parameters, including the number and distribution of flowers, CH fraction, and plant size.ResultsWe found that stressed plants show an increased tendency for self-pollination and a deficit in floral and vegetative development. However, when parentally primed, stressed plants show a milder response. Un-stressed offspring of stressed parents show reversed responses and exhibit an increased tendency to outcross, and improve floral and vegetative development.ConclusionsIn summary, we found that stress affects the reproduction strategy in the plants that experienced the stress and in subsequent offspring through F2 generation. Our results provide experimental evidence supporting a transgenerational extension to the theories of fitness associate sex and dispersal, where an individual’s tendency for sex and dispersal may depend on the stress experienced by its parents.

Extended one-generation reproductive toxicity study of food-grade titanium dioxide E171 with emphasis on reproductive and endocrine endpoints

Food-grade titanium dioxide E171 was administered in feed to Sprague Dawley rats in an extended one-generation reproductive toxicity (EOGRT) study (OECD Test 443). The dosed diet (0, 100, 300, or 1000 mg/kg body weight/day) started 10 weeks before mating and continued throughout the study. After weaning, pups were allocated to Cohorts 1 A/1B (to assess reproductive toxicity), 2 A/2B (to assess developmental neurotoxicity), and 3 (to assess developmental immunotoxicity); in addition, Cohort 1B was mated to produce an F2 generation and satellite F0 animals were evaluated for colonic aberrant crypt foci (ACF). In F0 animals, there were no systemic toxicity or reproductive effects, no treatment-related histopathological changes, and no ACF in the colon. Serum estradiol or testosterone concentrations were not changed in F0 or F1 animals. No pre-/postnatal developmental changes related to treatment were noted in F1 animals, and the reproductive performance of F1 Cohort 1B animals was unaffected. F2 pups showed no abnormalities in pre- or postnatal development (postnatal days 4–8). No treatment-related developmental neurotoxicity was observed in Cohorts 2 A/2B. Although no treatment-related immunotoxicity was observed in Cohort 3, the positive control did not induce the expected response; this segment of the study will be repeated. Analyses of blood and urine showed negligible systemic absorption of E171 from the gastrointestinal tract upon dietary ingestion. The no observed adverse effect level (NOAEL) for parental systemic toxicity, reproductive toxicity, offspring toxicity, and developmental neurotoxicity was considered 1000 mg/kg body weight/day. For developmental immunotoxicity, a NOAEL was not determined owing to insufficient T-cell-dependent antibody response in the positive control. Our study provides robust data on the reproductive toxicity and preneoplastic potential of E171.

Psychological health among adult offspring of lesbian parents at a time of anti-LGBTQ+ oppression

ABSTRACT This study investigates potential differences in psychological health (i.e. life satisfaction, anticipated future life satisfaction, distress), social well-being, and experiences of victimisation among adult offspring born to lesbian parents when compared with participants from a nationally representative sample surveyed in the same historical context of renewed anti-LGBTQ+ oppression. The research involved 75 adult offspring (M = 30.93, SD = 0.93; sex assigned at birth: 39 female and 36 male; gender identity: 73 cisgender and 2 gender nonbinary; sexual orientation: 51 heterosexual and 24 sexual minority) of the first generation conceived through donor insemination by lesbian parents. These offspring were matched with 75 participants of a U.S. probability sample based on several factors, including age, race/ethnicity, education, sex assigned at birth, gender identity, and sexual orientation. The comparison group is presumed to have been raised by heterosexual parents. After applying Bonferroni’s correction to minimise the risk of Type I errors resulting from multiple comparisons, no significant differences emerged in the study variables between the two samples. Despite a climate of renewed anti-LGBTQ+ oppression, adult offspring of lesbian parents were doing well, possibly due to unique socialisation processes in childhood when their parents taught them to be resilient even in the face of socio-environmental challenges.

Acetylcholinesterase Inhibitor Ameliorates Early Cardiometabolic Disorders in Fructose-Overloaded Rat Offspring.

We investigate the role of galantamine on autonomic dysfunction associated with early cardiometabolic dysfunction in the offspring of fructose-overloaded rats. Wistar rats received fructose diluted in drinking water (10%) or water for 60 days prior to mating. Fructose overload was maintained until the end of lactation. The offspring (21 days after birth) of control and fructose-overloaded animals were divided into three groups: control (C), fructose (F) and fructose + galantamine (GAL). GAL (5 mg/kg) was administered orally until the offspring were 51 days old. Metabolic, hemodynamic and cardiovascular autonomic modulation were evaluated. The F group showed decreased insulin tolerance (KITT) compared to the C and GAL groups. The F group, in comparison to the C group, had increased arterial blood pressure, heart rate and sympathovagal balance (LF/HF ratio) and a low-frequency band of systolic arterial pressure (LF-SAP). The GAL group, in comparison to the F group, showed increased vagally mediated RMSSD index, a high-frequency band (HF-PI) and decreased LF/HF ratio and variance in SAP (VAR-SAP) and LF-SAP. Correlations were found between HF-PI and KITT (r = 0.60), heart rate (r = -0.65) and MAP (r = -0.71). GAL treatment significantly improved cardiovascular autonomic modulation, which was associated with the amelioration of cardiometabolic dysfunction in offspring of parents exposed to chronic fructose consumption.

Local versus regional patterns in zoospore dispersal of the kelp Eisenia bicyclis (Laminariales, Phaeophyceae)

SummaryIt is generally accepted that kelp populations have a metapopulation structure. Most zoospores settle near to their parent individual, and infrequent but long‐distance dispersal of zoospores contributes to gene flow between local populations. Population genetic analysis of single nucleotide polymorphism genotyping by MIG‐seq (i.e. multiplexed inter‐simple sequence repeats genotyping by sequencing) was performed on the dominant kelp, Eisenia bicyclis, in two areas: Kitsunezaki (a sheltered area) and Shimoda (an exposed site). Regional scale analysis of genetic structure was conducted at six sites in Kitsunezaki and three sites in Shimoda. When viewed on a regional scale based on the inbreeding coefficient within the local population, the inbreeding ratio was higher in Shimoda than in Kitsunezaki, probably as a result of the limited vertical zonal distribution in the exposed environment. Vertically wide distribution in the sheltered environment apparently enabled frequent crossing among individuals in Kitsunezaki. By contrast, when viewed on a local scale based on the pairwise kinship coefficient (FST) between populations, gene flow among local populations in Shimoda occurred over a wide area, but was limited in Kitsunezaki. In Shimoda, genetic exchange between local populations, even if inbreeding is locally active, is likely to support metapopulation maintenance and rapid recovery of local populations. In Kitsunezaki, however, genetic exchange among local populations is limited within few 100 m, and the metapopulation structure will decline in the long term because of inbreeding depression. Local dispersal distance of zoospores was investigated based on parent–offspring analysis in the Kitsunezaki population, which revealed that zoospores mainly settled within 5 m of their parent. However, some zoospores traveled over 27 m within the 4 × 30 m study area. The present study shows the importance of examination at different spatial scales when investigating zoospore dispersal of laminarialean kelps.

Risk of Neurodevelopmental Disorders in Offspring of Parents with Major Depressive Disorder: A Birth Cohort Study.

Studies have reported inconsistent results regarding associations between parental depression and offspring neurodevelopmental disorders, such as developmental delay and autism spectrum disorder (ASD). In all, 7,593 children who were born between 1996 and 2010 in Taiwan and had at least one parent with major depressive disorder and 75,930 birth-year- and sex-matched children of parents without major depressive disorder were followed from 1996 or time of birth to the end of 2011. Intergroup differences in neurodevelopmental conditions-including ASD, attention-deficit hyperactivity disorder (ADHD), tic disorder, developmental delay, and intellectual disability (ID)-were assessed. Compared with the children in the control group, the children of parents with major depression were more likely [hazard ratio (HR), 95% confidence interval (CI)] to develop ADHD (1.98, 1.80-2.18), ASD (1.52, 1.16-1.94), tic disorder (1.40, 1.08-1.81), developmental delay (1.32, 1.20-1.45), and ID (1.26, 1.02-1.55). Parental depression was associated with offspring neurodevelopmental disorders, specifically ASD, ADHD, developmental delay, ID, and tic disorder. Therefore, clinicians should closely monitor the neurodevelopmental conditions of children of parents with depression.

Non-linear development of brain morphometry in child and adolescent offspring of individuals with bipolar disorder or schizophrenia

Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at increased risk of developing psychopathology. Structural brain alterations have been found in child and adolescent offspring of patients with bipolar disorder and schizophrenia, but the developmental trajectories of brain anatomy in this high-familial-risk population are still unclear. 300 T1-weighted scans were obtained of 187 offspring of at least one parent diagnosed with bipolar disorder (n=80) or schizophrenia (n=53) and offspring of parents without severe mental illness (n=54). The age range was 8 to 23 years old; 113 offspring underwent two scans. Global brain measures and regional cortical thickness and surface area were computed. A generalized additive mixed model was used to capture non-linear age trajectories. Offspring of parents with schizophrenia had smaller total brain volume than offspring of parents with bipolar disorder (d=-0.20, p=0.004) and control offspring (d=-0.22, p=0.005) and lower mean cortical thickness than control offspring (d=-0.23, p<0.001). Offspring of parents with schizophrenia showed differential age trajectories of mean cortical thickness and cerebral white matter volume compared with control offspring (both p’s=0.003). Regionally, offspring of parents with schizophrenia had a significantly different trajectory of cortical thickness in the middle temporal gyrus versus control offspring (p<0.001) and bipolar disorder offspring (p=0.001), which was no longer significant after correcting for mean cortical thickness. These findings suggest that particularly familial high risk of schizophrenia is related to reductions and deviating developmental trajectories of global brain structure measures, which were not driven by specific regions.

Comparing cognition in parents with schizophrenia or bipolar disorder and their 7-year-old offspring

Individuals with schizophrenia (SZ) or bipolar disorder (BP) display cognitive impairments, while their first-degree relatives perform at an intermediate level between the patient groups and controls. However, the environmental impact of having an ill relative likely varies with the type of kinship and some studies suggest that offspring may be particularly disadvantaged. The present study aimed to investigate the relationship between parent and child cognition in parents with SZ or BD and their 7-year-old offspring. A population-based cohort of 522 children (parental SZ, n = 202; parental BP, n = 120; controls, n = 200) and their parents underwent the same assessment battery covering a wide range of cognitive functions. We used Bayesian statistics to model performance. We found that performance on non-verbal tests was better in offspring than parents with SZ or BP, using the controls as reference. However, for verbal tests, there was little to no evidence for this pattern or even some evidence for the opposite in the BP group: relatively better performance in parents than offspring. The findings suggest that the offspring of parents with SZ or BP may be particularly disadvantaged in verbal abilities. Future studies will show whether this pattern persists throughout development.

The perceived social support of parents having bipolar disorder impacts their children’s mental health: a 10-year longitudinal study

BackgroundThe offspring of parents with bipolar disorder (OBD) are at higher risk of developing psychopathology than the offspring of parents with no affective disorder (control). In addition to genetic predisposition, childhood adversity and a stressful family environment are important risk factors for the OBD. Protective factors in parents, such as social support and coping strategies, may buffer the effects of stress on at-risk children. This study tested whether parents’ social support and coping style attenuated the link between risk status (OBD vs. control) and psychopathology in offspring.MethodsDuring offspring’s middle childhood, parents underwent a diagnostic interview and completed social support and coping style questionnaires. Sixty-nine OBD (39 female) and 69 control (29 female) offspring between ages 13 and 29 completed a diagnostic interview approximately 10 years later.ResultsParents’ social support satisfaction moderated the link between offspring risk status and their development of substance use disorder (SUD) symptoms (F(1,131) = 5.90, p = .017). Parents’ social network size moderated the link between offspring risk status and their development of anxiety and depression symptoms in an unexpected direction (F(1,131) = 5.07, p = .026). No effects of parents’ coping style were found.ConclusionsAmong the OBD, having parents with greater social support satisfaction and, unexpectedly, a smaller social network buffered their development of SUD and depression and anxiety symptoms by early adulthood. Parents’ social support may thus have a protective function for children in these high-risk families.

Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model.

Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated β-galactosidase activity. Strikingly, in the male offspring, we observe an interaction between maternal and paternal alcohol use, with histological indicators of accelerated age-related liver disease in the dual-parental offspring exceeding those induced by either maternal or paternal alcohol use alone. Our studies indicate that chronic parental alcohol use causes enduring mitochondrial dysfunction in offspring, resulting in a reduced NAD+/NAHD ratio and altered expression of the NAD+-dependent deacetylases SIRT1 and SIRT3. These observations suggest that some aspects of FASDs may be linked to accelerated aging due to programmed changes in the regulation of mitochondrial function and cellular bioenergetics.

Comparison of isometric handgrip test among pregnant offspring of hypertensive parents and pregnant offspring of non-hypertensive parents.

A family history of hypertension is one of the important risk factors for the development of pregnancy-induced hypertension (PIH). Offspring of hypertensive parents should be screened for PIH. The isometric handgrip (IHG) test is used to assess autonomic function among them. Autonomic function dysregulation can indicate their predisposition to develop PIH later in the course of pregnancy. To compare the IHG among pregnant offspring of hypertensive parents (Group 1) and non-hypertensive parents (Group 2). This is a cross-sectional study done among 100 pregnant women in the second trimester (50 participants in each group). Blood pressure responses to sustained hand grip for 2 minutes of maximum voluntary contraction (MVC) were recorded, immediately at the end of the IHG test and after 5 minutes of the IHG test. Independent t-test and Mann-Whitney U test were used to compare the responses in two groups. There is no statistical difference in basal blood pressure and heart rate between the two groups. Group 1 exhibited a significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to Group 2 immediately after 2 minutes of the IHG test. There is a significant increase in SBP after 5 minutes of the IHG in Group 2. Offspring of hypertensive parents have increased sympathetic reactivity and restoration of the blood pressure is significantly less compared to offspring of normotensive parents, which may predispose them for PIH. IHG can be applied as a convenient tool to screen the population who are at risk of PIH in places like primary health centres or field screenings where IHG is one possible option.

Behavioral skill practice as a predictor of mood and family functioning in adolescents with bipolar and depressive mood disorders: Results of a 6-month randomized trial of family-focused therapy.

Behavioral interventions require considerable practice of treatment skills in between therapy sessions. The effects of these treatments may vary with the degree to which patients are able to implement these practices. In offspring of parents with bipolar and major depressive disorders, we examined whether youth who frequently practiced communication and problem-solving skills between family-focused therapy (FFT) sessions had less severe mood symptoms and better psychosocial functioning over 6 months than youth who practiced less frequently. We randomly assigned offspring (ages 12-19) of parents with mood disorders to 12 sessions of FFT plus a mobile app that encouraged the practice of communication, problem-solving and mood management skills (FFT-MyCoachConnect [MCC] condition) or 12 sessions of FFT with an app that only allowed for tracking of symptoms and stress (FFT-Track condition). Independent evaluators assessed youths' mood and psychosocial functioning at 9-week intervals over 27 weeks. Clinicians rated participants' between-session skill practice at each FFT session. FFT-MCC was associated with more frequent skill practice than FFT-Track over 18 weeks of treatment. Skill practice was associated with reductions in youths' mood instability and perceptions of family conflict over 27 weeks in both app conditions. Skill practice mediated the effects of app condition on youths' mood instability and family functioning. Mobile applications as adjuncts to family therapy for youth with mood disorders can help increase skill practice. These findings provide preliminary causal evidence for behavioral skill practice improving mood symptoms and family functioning among youth with mood disorders.

Genome-Wide Association Analyses and Population Verification Highlight the Potential Genetic Basis of Horned Morphology during Polled Selection in Tibetan Sheep.

The types and morphology of sheep horns have been extensively researched, yet the genetic foundation underlying the emergence of diverse horn characteristics during the breeding of polled Tibetan sheep has remained elusive. Genome-wide association analysis (GWAS) was performed on 103 subtypes (normal large horn, scurs, and polled) differentiated from G2 (offspring (G2) of parent (G1) of polled) of the polled core herd. Six single nucleotide polymorphisms (SNPs) located on chromosome 10 of the relaxin family peptide receptor 2 (RXFP2) gene exhibited positive correlations with horn length, horn base circumference, and horn base interval. Furthermore, in genotyping 382 G2 individuals, significant variations were observed for each specific horn type. Three additional mutations were identified near the target SNP upstream of the amplification product. Finally, the RXFP2-specific haplotype associated with the horned trait effectively maintained horn length, horn base circumference, and horn base interval in Tibetan sheep, as confirmed by population validation of nine loci in a sample size of 1125 individuals. The present study offers novel insights into the genetic differentiation of the horned type during improvement breeding and evolution, thereby establishing a robust theoretical foundation for polled Tibetan sheep breeding and providing valuable guidance for practical production.

Evaluation of brachycephalic obstructive airway syndrome breeding test results in Finland from 2017 to 2022

BackgroundBrachycephalic obstructive airway syndrome (BOAS), observed in many flat-faced dog breeds, is one of the most urgent welfare problems in pedigree dogs. Various breeding schemes against BOAS have been implemented in many countries during recent years, but their impact on breed health remains unknown. The BOAS breeding test, used by the Finnish Kennel Club (FKC), includes an exercise component with a recovery assessment, BOAS grading by a veterinarian that evaluates upper respiratory signs before and after exercise, and a nostril stenosis assessment. The aim of our study was to evaluate BOAS breeding test results and estimate the heritability of the BOAS grade using parent–offspring regression from FKC data collected during 2017–2022.ResultsThe majority (80%) of dogs (n = 957) participating in FKC BOAS testing were English Bulldogs, French Bulldogs, and Pugs. In 2022, 89–100% of the litters from these three breeds registered with the FKC had at least one parent tested for BOAS. The proportion of dogs failing the exercise test was highest in English Bulldogs (11%), followed by French Bulldogs (4%) and Pugs (3%). In these three breeds, moderate to severe BOAS signs were reported in 28%, 22% and 30% of dogs, respectively. The proportion of moderate to severe nostril stenosis was highest (71%) in Pugs, followed by French Bulldogs (55%), and English Bulldogs (40%). Estimates of heritability for BOAS grade were separately calculated for these three breeds and for all dogs, and the estimates were moderate to high, ranging from 0.39 to 0.58.ConclusionsThe exercise test alone did not sufficiently identify dogs with moderate to severe BOAS signs. To better consider the complex nature of BOAS and breed differences, exercise tolerance, the severity of upper respiratory signs (BOAS grade) and nostril stenosis should all be assessed together in breeding animals. The heritability estimates for veterinary-assessed BOAS grade indicated that BOAS grade could be used in selective breeding to obtain less-affected offspring.

Insulin resistance is associated to future hypertension in normotensive salt-sensitive individuals: a 10-year follow-up study.

Salt-sensitive hypertension is associated with insulin resistance in nonobese individuals. However, no data have been reported for normotensive offspring of hypertensive salt-sensitive parents. To evaluate in normotensive salt-sensitive or salt-resistant offspring of hypertensive parents (offSS-HT and offSR-HT, respectively): the possible association between insulin resistance and endothelial dysfunction, and the risk of developing hypertension in a 10-year follow-up. Forty-one offSS-HT (29 ± 2 years; 20 female) and 36 offSR-HT (25 ± 3 years; 16 female) were followed up for 10 years. Both groups were considered lean. At baseline, creatinine clearance (CrCl), 24 h urinary albumin excretion (UAE), glycemia, and insulinemia were measured before and after 60 and 120 min of glucose overload (75 g). HOMA Index and the area under the curve (AUC) were calculated. Blood pressure (BP) and 24 h urine sodium excretion was measured annually. Postischemic minimum vascular resistance (forearm plethysmography) was assessed at baseline. In offSS-HT, UAE (53 ± 3 mg/min) and CrCl (136 ± 8 ml/min) were higher in offSS-HT than in offSR-HT. (UAE: 12 ± 4 mg.min; p,0.01 and CrCl 107 ± 6 ml.min; P < 0.01). An impaired vasodilatory postischemic response was observed in offSS-HT compared with offSR-HT ( P < 0.01). In offSS-HT glycemia, insulin, AUC at 69 and 120 min post OTG were greater than in offSR-HT, p < 0.02. In offSS-HT, blood pressure rose ( P < 0.01) the 10 years follow-up compared with offSR-HT. Salt sensitivity in the offspring of hypertensive salt-sensitive individuals is associated with insulin resistance and endothelial dysfunction and is prone to hypertension over a short period of time.

High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases

BackgroundGenetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis.MethodsWe conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation.ResultsOur CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications.ConclusionCES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Parental Inflammatory Bowel Disease with Child Autism: A Comprehensive Review and Meta-Analysis.

Inflammatory bowel disease (IBD) has been shown to be connected to a greater possibility of neurologically developed problems, such as autism spectrum disorders (ASDs). However, the proof linking parental IBD with ASD in offspring is inconclusive. Thus, we carried out a meta-analysis and comprehensive review to elucidate such linking. Prior research was identified through reviewing multiple internet-based sources, including Cochrane, Web of Knowledge, Embase, CINAHL, PubMed, and PsycINFO, from 1960 to December 2022. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were determined employing random-effects models, in spite of the I2 statistic measurement of heterogeneity. Prediction intervals (PIs) have been presented to allow for more useful inferences and to indicate the range of genuine effects that might be predicted in future scenarios. Six studies (two case-control studies and four cohort studies) involving 3,200,199 participants were incorporated into the meta-analysis. The pooled RRs of ASDs among offspring of IBD parents were 1.15 (95% CI, 0.92 to 1.45, P = 0.226; I2 = 81.4%, P = 0.003; PI, 0.53-2.62), indicating no significant connection between parental IBD and the likelihood of ASDs in children. Type of IBD, and sex both also yielded no statistically significant results according to subgroup analysis. Our meta-analysis does not provide evidence that parental IBD is connected with the elevated likelihood of ASDs in their children. To confirm these results and understand their underlying mechanisms, additional research with larger sample sizes and improved study designs is required.